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Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals

Rivera, Margarita, Locke, Adam E., Corre, Tanguy, Czamara, Darina, Wolf, Christiane, Ching-Lopez, Ana, Milaneschi, Yuri, Kloiber, Stefan, Cohen-Woods, Sara, Rucker, James, Aitchison, Katherine J., Bergmann, Sven, Boomsma, Dorret I., Craddock, Nick ORCID:, Gill, Michael, Holsboer, Florian, Hottenga, Jouke-Jan, Korszun, Ania, Kutalik, Zoltan, Lucae, Susanne, Maier, Wolfgang, Mors, Ole, Müller-Myhsok, Bertram, Owen, Michael J. ORCID:, Penninx, Brenda W. J. H., Preisig, Martin, Rice, John, Rietschel, Marcella, Tozzi, Federica, Uher, Rudolf, Vollenweider, Peter, Waeber, Gerard, Willemsen, Gonneke, Craig, Ian W., Farmer, Anne E., Lewis, Cathryn M., Breen, Gerome and McGuffin, Peter 2017. Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals. British Journal of Psychiatry 211 (2) , pp. 70-76. 10.1192/bjp.bp.116.183475

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Background Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT. Results In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO. Conclusions This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Cambridge University Press
ISSN: 0007-1250
Date of First Compliant Deposit: 13 September 2017
Date of Acceptance: 13 March 2017
Last Modified: 11 Oct 2023 19:51

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